Melanoma heterogeneity: differential, invasive, metastatic properties and profiles of cathepsin B, D and L activities in subclones of the B16F10-NEX22 cell line

Melanoma heterogeneity: differential, invasive, metastatic properties and profiles of cathepsin B, D and L activities in subclones of the B16F10-NEX22 cell line

Author Freitas, ZFO Google Scholar
Rodrigues, E. G. Google Scholar
Oliveira, V Google Scholar
Carmona, A. K. Google Scholar
Travassos, L. R. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Tumour cell lines and in vivo growing tumours are heterogeneous, comprising different cell clones. To understand why some cells primarily invade a tissue, while others are more apt to metastasize, several clones from the established B16F10-Nex2 cell line were isolated and 105 viable cells of each clone were injected intravenously into C57B1/6 and Balb/c mice. Two cell clones (Nex2B and Nex2D) showed contrasting metastatic abilities. Clone 2D rather than clone 2B colonized the lungs of both mice after intravenous injection. Surprisingly, clone 2B grew more rapidly than 2D after subcutaneous implantation, significantly reducing the survival of injected mice. Clearly, dissociation between subcutaneous growth and metastatic ability was observed in clones from the same tumour cell lineage. Clone Nex2B continuously released proteolytic activity, including cathepsin B, and showed a greater capacity to invade Matrigel than clone Nex2D. Clone Nex2D accumulated cathepsins B, D and L intracellularly and released a moderate proteolytic activity in vitro that was inhibited with the time of incubation. E-64-treated Nex2B cells injected subcutaneously showed a significant delay in tumour development and increased survival of challenged animals. A similar result was obtained on treatment of clone 2B with chagasin, a cysteine proteinase inhibitor from Trypanosoma cruzi, even at 2 muM. Clone Nex2D was less sensitive to pretreatment with inhibitors of cysteine proteases for tumour development in vivo. Our results suggest that, in a tumour cell population, cells dissociate into metastatic and non-metastatic subtypes, and that release or accumulation of cathepsins can be a differential trait of these cells. (C) 2004 Lippincott Williams Wilkins.
Keywords B16F10 melanoma
cathepsins
clones
metastasis
tissue invasion
Language English
Date 2004-10-01
Published in Melanoma Research. Philadelphia: Lippincott Williams & Wilkins, v. 14, n. 5, p. 333-344, 2004.
ISSN 0960-8931 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 333-344
Origin http://dx.doi.org/10.1097/00008390-200410000-00002
Access rights Closed access
Type Article
Web of Science ID WOS:000224649600002
URI http://repositorio.unifesp.br/handle/11600/27976

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